Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou 225009, China.
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou 225009, China.
Molecules. 2024 Sep 15;29(18):4389. doi: 10.3390/molecules29184389.
A bioactivity-guided separation strategy was used to identify novel antistroke compounds from (L.) R. Br., a medicinal plant. As a result, 4 undescribed compounds (, , and ) and 13 known compounds, including 1 new natural product (), were isolated from The structures of these compounds were elucidated through comprehensive spectroscopic techniques, such as 1D/2D nuclear magnetic resonance (NMR) spectroscopy, high-resolution electrospray ionization mass spectrometry (HRESIMS), and quantum chemical calculations. An oxygen-glucose deprivation/reoxygenation (OGD/R)-injured rat pheochromocytoma (PC12) cell model was used to evaluate the antistroke effects of the isolates. Compounds , , , and provided varying degrees of protection against OGD/R injury in the PC12 cells at concentrations of 12.5, 25, and 50 µM. Among the tested compounds, compound demonstrated the most potent neuroprotective effect, which was equivalent to that of the positive control drug (edaravone). Then, transcriptomic and bioinformatics analyses were conducted to reveal the regulatory effect of compound on gene expression. In addition, quantitative real-time PCR (qPCR) was performed to verify the results of the transcriptomic and bioinformatics analyses. These results suggest that the in vitro antistroke effect of compound may be associated with the regulation of the gene. Thus, compound is a promising candidate for the development of novel antistroke drugs derived from natural products, and this topic should be further studied.
采用生物活性导向分离策略,从药用植物 (L.)R. Br. 中鉴定出新型抗中风化合物。结果,从 中分离出 4 个未描述的化合物(、、和)和 13 个已知化合物,包括 1 个新的天然产物()。这些化合物的结构通过综合光谱技术,如 1D/2D 核磁共振(NMR)光谱、高分辨率电喷雾电离质谱(HRESIMS)和量子化学计算来阐明。采用氧葡萄糖剥夺/再氧合(OGD/R)损伤大鼠嗜铬细胞瘤(PC12)细胞模型来评价分离物的抗中风作用。在 12.5、25 和 50 μM 浓度下,化合物 、、、对 OGD/R 损伤的 PC12 细胞具有不同程度的保护作用。在所测试的化合物中,化合物 表现出最强的神经保护作用,与阳性对照药物(依达拉奉)相当。然后,进行转录组学和生物信息学分析以揭示化合物 对基因表达的调节作用。此外,进行实时定量 PCR(qPCR)以验证转录组学和生物信息学分析的结果。这些结果表明,化合物 的体外抗中风作用可能与 基因的调节有关。因此,化合物 是一种有前途的候选药物,可用于开发源自天然产物的新型抗中风药物,应进一步研究该课题。